Inspections, Compliance, Enforcement, and Criminal Investigations
Kabco Pharmaceuticals, Inc. 11/10/10
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
New York District
November 10, 2010
WARNING LETTER NYK-2011-09
Via United Parcel Service
Abu Kabir, CEO and President
Kabco Pharmaceuticals, Inc.
2000 New Horizons Blvd.
Amityville, New York 11701
Dear Mr. Kabir:
On June 21 through June 24, 2010 and July 7,2010 the U.S. Food and Drug Administration (FDA) inspected your facility located at 2000 New Horizons Blvd., Amityville, New York. Your firm manufactures, packages, labels, and holds dietary supplements. Our investigators found a number of violations of 21 CFR Part 111, Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements.
The inspection revealed that your (b)(4) Tablet, (b)(4) Capsule, (b)(4) Tablet, and (b)(4) Capsule dietary supplement products manufactured in your facility, are adulterated within the meaning of Section 402(g)(1) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 342(g)(1)] in that the dietary supplements have been prepared, packed, or held under conditions that do not meet current good manufacturing practice regulations for dietary supplements. These observations were presented to you in a FDA 483 at the conclusion of our inspection on July 7, 2010.
The inspection revealed the following deficiencies:
1. You failed to determine whether specifications are met before use of components as required by 21 CFR 111.75(a). Specifically,
• You failed to conduct at least one appropriate test or examination to verify identity of a dietary ingredient prior to its use. From the time period between June 25 and October 6, 2009, you did not perform identity testing on any dietary ingredients that you received, and during the time period between October 6, 2009 and May 10, 2010 you only performed identity testing on randomly selected dietary ingredients. Examples of some of the dietary ingredients that you failed to test include, but are not limited to the following: L-carnitine (used to manufacture (b)(4) Tablet Lot (b)(4), valerian root (used to manufacture (b)(4) Capsules Lot (b)(4) and ginkgo biloba leaf extract (used to manufacture (b)(4) Lot (b)(4) ).
• You failed to qualify suppliers of components (other than dietary ingredients) by establishing the reliability of the suppliers' certificate of analyses through confirmation of the results of their tests or exams, prior to their use. During the time period of June 25, 2009 through May 10, 2010, your firm did not qualify suppliers of any such components by establishing the reliability of the suppliers' certificate of analyses. Examples of some of the suppliers that you failed to qualify include, but are not limited to, the following: (b)(4) (supplier of D-calcium pantothenate), (b)(4) (supplier of Magnesium Stearate), and (b)(4) supplier of L-Selenomethionine).
We acknowledge receipt of your July 21, 2010 response to the FDA 483; however it does not adequately address your failure to conduct at least one appropriate test or examination to verify the identity of dietary ingredients prior to their use or your failure to qualify your suppliers of components other than dietary ingredients by establishing the reliability of the certificate of analyses through confirmation of the results of suppliers' tests or examinations. You stated that you had started conducting identity testing for all incoming raw materials after April 5, 2010 and were currently testing the materials that had not been previously tested. You also stated that you were developing methods to inspect and qualify the vendors/suppliers of the packaging components and expect to be in compliance within 60 days of the date of your response. Your responses are inadequate because you did not provide documentation that you began identity testing on April 5, 2010 as stated in your response and you did not provide a completion date for the identification of the dietary ingredients in your warehouse that had not been previously tested. In addition, you did not indicate what steps you intend to take regarding already distributed dietary supplements, which were manufactured using dietary ingredients and other components for which your firm did not conduct identity testing or for which you failed to qualify the suppliers, as applicable. We acknowledge that you are not required to continue qualifying the suppliers of your components if you are currently conducting appropriate tests or examinations on all such components.
2. You failed to include in your master manufacturing record (MMR), the following elements required by 21 CFR 111.210:
• The weight or measure of each dietary ingredient and component used in the production of your (b)(4) Tablet (Lot (b)(4)) and (b)(4) Capsule (Lot (b)(4) ) as required by 21 CFR 111.210(a) and 21 CFR 111.210(c).
• Procedures for sampling in the MMRs for (b)(4) Tablet (Lot (b)(4)), (b)(4) Capsule (Lot (b)(4)), (b)(4) Tablet (Lot (b)(4)), and (b)(4) Capsule (Lot (b)(4) ), as required by 21 CFR 111.210(h)(2).
Your July 21, 2010 response states that you have revised the master manufacturing/batch record to include an additional column to record the quantity of the dietary ingredients and components weighed by the operator, updated your SOP to include the procedures for sampling the finished product and trained your supervisors and operators to collect such samples. Your responses are inadequate because you did not provide the revised master manufacturing/batch record or the updated SOP for sampling of in process points and finished product. In addition, the documentation of training provided did not appear to address collection of samples.
3. Your batch production records (BPR) did not include complete information as required by 21 CFR 111.255(b) and 21 CFR 111.260. Specifically,
• Your BPR for (b)(4) Tablets (Lot (b)(4)), (b)(4) Capsules (Lot (b)(4)), (b)(4) Tablet (Lot (b)(4)), and (b)(4) Capsules (Lot (b)(4)) contain numerous omissions and errors such as missing supervisor signatures, use of white out, missing data, incorrect units of measure, and misplacement of decimal points.
Also, your batch production records (BPR) did not include documentation at the time of performance that quality control reviewed the BPR for the results of any tests and examinations on the finished batches of dietary supplements and approved and released, or rejected the batches for distribution to comply with 21 CFR 111.260(1)(1)(ii) and 21 CFR 111.260(1)(3). Specifically,
• Your BPR does not contain documentation at the time of performance that quality control personnel reviewed the results of tests and examinations conducted on finished batches of dietary supplements before releasing the product. For example, the Bill of Lading (No. (b)(4)) for was signed off on for shipment to the customer on 05/06/2010, however, the analytical testing, including the physio-chemical specifications results, were not approved until 05/07/2010.
Your July 21, 2010 response states that you have trained all supervisors and QA personnel to review the batch records for accurate as well as complete information, that the SOP was updated "to accommodate" instances when the QA manager did not sign for approval of testing results until after the finished dietary supplement was released for distribution, and that your QA personnel would be trained in such procedures. Your response is not adequate because under 21 CFR 111.123(b)(1), quality control must not approve and release for
distribution any batch of dietary supplement for which any component in the batch does not meet its identity specification and, under 21 CFR 111.123(b)(2), quality control must not approve and release for distribution any batch of dietary supplement for which the batch does not meet the product specifications established in 21 CFR 111.70(e).
4. You failed to use effective measures to protect against the inclusion of metals or other foreign material in your dietary supplements as required by 21 CFR 111.365(i). Specifically, on June 21, 2010, our investigators observed the dietary supplement (b)(4) Capsules (Lot (b)(4)) on a conveyor belt packaging line without passing through a metal detector, which is the manner in which your firm chooses to comply with 21 CFR 111.365(i).
Your July 21, 2010 response states that you re-inspected the (b)(4) Capsules (Lot (b)(4)) through an inspection belt equipped with metal detecting equipment on June 21, 2010; you have decided to install metal detecting equipment on your remaining inspection belts; and will not use any inspection belts until the installation of metal detecting equipment is completed. Your response is not adequate because you did not provide documentation that (b)(4) Capsules (Lot (b)(4)) were re-inspected through metal detecting equipment on June 21, 2010; you did not provide documentation that metal detecting equipment was installed on remaining inspection belts or provide a date for compliance; and you did not address how you will prevent the passage of dietary supplement product through inspection belts without functioning metal detecting equipment in the future.
5. You failed to meet the requirements for holding and distributing under Subpart M of the CGMP [21 CFR 111.453 - 21 CFR 111.475]. Specifically,
• You did not follow written procedures for holding and distributing operations as required by 21 CFR 111.453. For example, on June 21, 2010, our investigators noted that the following components did not have a status label: Spirulina Pacifica (b)(4), Tri Tab Gyean (b)(4), Hydrous Calcium Sulfate (b)(4), and Calcium Citrate (b)(4). Also the component Calcium Ascorbate (b)(4) had the incorrect status label (b)(4) applied to it. According to your SOP 11.16, (b)(4) product such as (b)(4) etc. You did not follow the procedures in this SOP.
• You failed to hold components, dietary supplements, packaging, and labels under conditions that do not lead to the mix-up, contamination, or deterioration of components, dietary supplements, packaging, and labels as required by 21 CFR 111.455(c). For example, on June 21, 2010 our investigator observed (b)(4) Caps (Batch (b)(4)) identified as (b)(4) but stored with (b)(4) raw materials.
Your July 21, 2010 response states that you have trained all receiving and warehouse personnel regarding the SOP to appropriately label all the materials with the proper status labels and to ensure storage of all raw materials at the designated storage area to avoid any mix-up, contamination, or deterioration. You also provided documentation of this training (Employee Training Record, Attachment 4 to your response) and your current SOP 11.16 (Revision Date: 3/27/2008). However, your response is not adequate because the Employee Training Record (Attachment 4 to your response) contains procedures, namely items 2-6, for which you did not provide corresponding updated SOPs for our evaluation.
6. You failed to fit each freezer, refrigerator, and other cold storage compartment you use to hold components or dietary supplements with an indicating thermometer, temperature measuring device, or temperature recording device that indicates and records, or allows for recording by hand, the temperature accurately within the compartment as required by 21 CFR 111.27(a)(5)(i). On June 21, 2010, our investigator noted that the refrigerator containing Probiotic (b)(4), Bifidobacterium lnfinitis (b)(4), Bifidobacterium Bifidum (b)(4) , NADH (b)(4), and L. Casei Subsp (b)(4) did not include an indicating thermometer or temperature-measuring device.
During the inspection, you told our investigator that you had replaced the refrigerator with a new refrigerator which included a thermometer. In your July 21, 2010 response letter, you stated that you have begun daily monitoring and recording of the temperature of the refrigerator used in storing heat sensitive raw materials as of June 23, 2010 and provided temperature monitoring records. We will verify the adequacy of your correction during the next inspection of your firm.
This letter is not an all-inclusive list of violations at your facility. It is your responsibility to ensure that your establishment and the products you market comply with the Act and all of its implementing regulations.
Failure to promptly correct the violations specified above may result in enforcement action without further notice. Enforcement action may include seizure of violative products and/or injunction against the manufacturers and distributors of violative products.
In addition to the violations above, we have the following comments. We also note that you failed to make and keep complete documentation of when cleaning of mixing equipment occurred, in accordance with your SOP for the Cleaning of Blending Equipment. You are required to keep documentation in individual equipment logs, of the date of use, maintenance, cleaning, and sanitizing of equipment unless such documentation is kept with the batch record as required by 21 CFR 111.35(b)(2). Specifically, your Equipment Cleaning and In-Process Log Record for (b)(4) for the time period of 03/27/10 through 03/30/10 does not document the type of cleaning (b)(4) performed between product runs. In your response dated July 21, 2010, you stated that you had revised the equipment cleaning record keeping of the mixing equipment, introduced in-process log records for mixers and an additional column was added to the record to identify (b)(4) major and minor cleaning of the mixing equipment. You should ensure that you maintain proper documentation of the cleaning of the mixing equipment.
Please advise this office in writing within 15 days from your receipt of this letter of the specific steps you have taken to correct the violations noted above and to ensure that similar violations do not occur in the future. Your response should include any documentation necessary to show that correction has been achieved. If you cannot complete all corrections before you respond, state the reason for the delay and the date by which you will complete the corrections.
Your written response should be sent to Dean R. Rugnetta, Compliance Officer, U.S. Food and Drug Administration, 300 Pearl Street, Suite 100, Buffalo, New York 14202. If you have any questions about this letter, please contact Compliance Officer Dean Rugnetta at (716) 541-0324 or Email at email@example.com.
Ronald M. Pace
New York District